Manufacture of Necator americanus as an infectious challenge agent: Accelerating human hookworm vaccine development

Authors

• Guacyara Erwin, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• Larissa Scholte, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• Rafaela Saes, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• Guangzhao Li, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• Linda Schellhaas, Quality Reviews, Inc., Falling Waters, WV, 25419, United States of America.
• Ramesh Ratnappan, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• David I. Pritchard, School of Pharmacy, University of Nottingham, Boots Sciences Building, University Park, Nottingham, NG7 2RD, UK.
• John Hawdon, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• David Diemert, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America; Department of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America.
• Jeffrey M. Bethony, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, 20052, United States of America. Electronic address: jbethony@gwu.edu.

Document Type

Journal Article

Publication Date

4-15-2025

Journal

Microbial pathogenesis

Volume

204

DOI

10.1016/j.micpath.2025.107592

Abstract

Hookworms infect 450 million people globally and account for the loss of 5 million disability-adjusted life years annually. Over the last decade, the Human Hookworm Vaccine (HHV) candidate N. americanus Glutathione-S-Transferase-1 (Na-GST-1) has advanced to efficacy testing. This manuscript describes the manufacture of third-stage N. americanus larvae (NaL3) as an infectious challenge agent to provide "proof-of-concept" for the efficacy of Na-GST-1 prior to more extensive and more resource-intensive vaccine field trials in hookworm endemic areas. NaL3 were produced from fecal samples of three hookworm-infected human donors by a modified Harada and Mori method that complied with current Good Manufacturing Practices (cGMP). A series of lot release tests assessed the purity (bioburden), viability (potency), and identity (speciation) of NaL3 before administration to participants in a hookworm vaccine challenge model (HVCM) in Washington, DC. Twenty-four production runs yielded an average of 947 NaL3 per lot, which were approved for clinical to inoculate of 39 participants in a Hookworm Vaccine Challenge Model. This manuscript describes the unique manufacture and testing for NaL3 in compliance with cGMP.

APA Citation

Erwin, Guacyara; Scholte, Larissa; Saes, Rafaela; Li, Guangzhao; Schellhaas, Linda; Ratnappan, Ramesh; Pritchard, David I.; Hawdon, John; Diemert, David; and Bethony, Jeffrey M., "Manufacture of Necator americanus as an infectious challenge agent: Accelerating human hookworm vaccine development" (2025). GW Authored Works. Paper 7045.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7045

Department

Microbiology, Immunology, and Tropical Medicine